Indications

• Humanized (5% murine) monoclonal IgG antibody that binds the C3 region of the IgE Fc region
• US (FDA):
  • Asthma
    • Adults and adolescents (≥12 years old) with moderate-severe persistent asthma who have a positive SPT or sIgE to a perennial aeroallergen and whose symptoms are inadequately controlled with ICS.
    • Total serum IgE levels should be between 30 and 700 IU/mL
  • Chronic idiopathic urticaria

• Europe:
  • Now eligible if baseline IgE 30-1500 IU/mL

Notes:

• Asthma patients with high eosinophil count (serum AEC >300/uL) may be more likely to have a good response
• Off-label uses include:
  • ABPA
  • Atopic dermatitis
  • Chronic rhinosinusitis with nasal polyps
  • Pre/co-medication for aeroallergen/venom/food immunotherapy to improve safety

Adverse Effects and Relative Contraindications

• Anaphylaxis – occurs in up to 0.2%, most commonly within first 3 doses and up to 2 hours after injection (but reported to occur even a year after starting omalizumab and hours after receiving injection)
  • If possible, discontinue beta-blockers before starting omalizumab
  • Unclear whether these reactions are caused by IgE sensitization to omalizumab or its excipients (sucrose, L-histidine, L-histidine hydrochloride monohydrate, and polysorbate 20) vs an alternative non–IgE-mediated mechanism
  • Skin testing protocols with omalizumab have been published (see references)
    
• Cardiovascular risk – FDA is evaluating interim safety findings from an ongoing study of Xolair that suggests an increased number of cardiovascular and cerebrovascular adverse events in a group of patients using Xolair vs. controls.
• Malignancy – small increase in risk (0.5% vs 0.2% in controls) but a subsequent long term safety analysis (EXCELS) demonstrated no increased risk
• Eosinophilic conditions – patients on Xolair may develop systemic eosinophilia syndrome with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually are associated with reduction of oral corticosteroid therapy.
• Serum-sickness like disease – arthritis/arthralgia, rash (urticaria or other forms), fever and lymphadenopathy with an onset 1–5 days after the first or subsequent injections of Xolair which may recur after additional doses in some patients. Stop Xolair if a patient develops this constellation of signs and symptoms.
• Parasitic infections – monitor patients at high risk of helminth infection while on Xolair therapy. Insufficient data are available to determine the length of monitoring for helminth infection after discontinuation of Xolair.
• Pregnancy and lactation – category B, administer Xolair during pregnancy only if clearly needed. Xolair may be secreted in breast milk, and possible harm to the infant is unknown, caution should be exercised when Xolair is administered to a nursing woman.

Consent

• Give patient medication information sheet
• Obtain written consent
  
  

  Xolair medication guide and consent.pdf
  

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Calculate Dose (Asthma)

• Determined by body weight and the levels of serum IgE (0.016 mg/kg per IU/mL of IgE per month)
• For omalizumab to cause a sufficient reduction in IgE levels (i.e., to a target level of <50 ng/mL), dosing needs to be at a molar excess of approximately 15-fold over baseline IgE. Based on these measurements, 75-600 mg of omalizumab may be needed for each administration, with a maximum recommended dose of 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union

US (FDA) Dosing Table

ICATA Study

• Pediatric dosing (6-20 years old) from the Inner-City Anti-IgE Therapy for Asthma (ICATA) Study

EU Novartis Dosing Table

Note: if patient calculated to receive omalizumab Q2 weeks but is unable to receive injections due to difficulty adhering to this schedule, can consider giving twice the dose once per month instead. For example, patient calculated to receive omalizumab 225 mg Q2 weeks may receive dose as 450 mg monthly

Administration

Monitoring

• Adverse effects
  • Due to risk of anaphylaxis, patients should receive treatment only under direct medical supervision and be observed in clinic after administration (see Omalizumab Joint Task Force report recommendations above)
  • Local injection site reaction - in 45% (vs 43% placebo), severe in 12%, most reactions occurred within 1 hour, lasted <8 days, and decreased in frequency with additional dosing.
  • Do not abruptly discontinue corticosteroids upon initiation of Xolair therapy (to avoid asthma exacerbation)

• Weight - adjust doses for significant changes in body weight (see Table 1 and Table 2).

• IgE levels
  • Total IgE level is elevated during treatment (3-6 fold) due to formation of anti-IgE IgG1:IgE complexes and remain elevated for up to 1 year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair treatment cannot be used as a guide for dose determination.
    • Interruptions <1 year: Dose based on serum IgE levels obtained at the initial dose determination.
    • Interruptions lasting >1 year: Re-test total serum IgE levels for dose determination.
  • Free IgE level may be helpful to monitor anti-IgE treatment; free IgE level drops >95% from baseline at 1st month of treatment.
    • 

      IBT free-IgE panel.pdf
      

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• Clinical response
  • Minimum of 12 weeks of treatment is needed to determine efficacy, and a 3-6 month trial is appropriate. Some patients may respond after 1 month.
  • UK responder algorithm
    

Discontinuation

• There are no well-established guidelines to help decide when/if omalizumab therapy can be discontinued
• Consider discontinuation if patient is not clinically responding (see above)
• Bob Lanier: discontinue at 2 years with full intent of re-institution if there is deterioriation

References